Arginine plays diverse roles in cellular physiology. As a semi-essential amino acid, arginine deprivation has been used to target cancers with arginine synthesis deficiency. Arginine-deprived cancer ...cells exhibit mitochondrial dysfunction, transcriptional reprogramming and eventual cell death. In this study, we show in prostate cancer cells that arginine acts as an epigenetic regulator to modulate histone acetylation, leading to global upregulation of nuclear-encoded oxidative phosphorylation (OXPHOS) genes. TEAD4 is retained in the nucleus by arginine, enhancing its recruitment to the promoter/enhancer regions of OXPHOS genes and mediating coordinated upregulation in a YAP1-independent but mTOR-dependent manner. Arginine also activates the expression of lysine acetyl-transferases and increases overall levels of acetylated histones and acetyl-CoA, facilitating TEAD4 recruitment. Silencing of TEAD4 suppresses OXPHOS functions and prostate cancer cell growth in vitro and in vivo. Given the strong correlation of TEAD4 expression and prostate carcinogenesis, targeting TEAD4 may be beneficially used to enhance arginine-deprivation therapy and prostate cancer therapy.
Arginine is an amino acid critically involved in multiple cellular processes including the syntheses of nitric oxide and polyamines, and is a direct activator of mTOR, a nutrient-sensing kinase ...strongly implicated in carcinogenesis. Yet, it is also considered as a non- or semi-essential amino acid, due to normal cells' intrinsic ability to synthesize arginine from citrulline and aspartate via ASS1 (argininosuccinate synthase 1) and ASL (argininosuccinate lyase). As such, arginine can be used as a dietary supplement and its depletion as a therapeutic strategy. Strikingly, in over 70% of tumors, ASS1 transcription is suppressed, rendering the cells addicted to external arginine, forming the basis of arginine-deprivation therapy. In this review, we will discuss arginine as a signaling metabolite, arginine's role in cancer metabolism, arginine as an epigenetic regulator, arginine as an immunomodulator, and arginine as a therapeutic target. We will also provide a comprehensive summary of ADI (arginine deiminase)-based arginine-deprivation preclinical studies and an update of clinical trials for ADI and arginase. The different cell killing mechanisms associated with various cancer types will also be described.
Aberrant expression of epidermal growth factor receptor (EGFR) is present in many human tumors. Several reports have shown that EGFR is translocated into the nucleus during liver regeneration and in ...several types of cells and tissues such as placenta and thyroid. Nuclear EGFR is associated with transcription, DNA synthesis, and DNA repair activity and serves as a prognostic marker in breast carcinoma and oropharyngeal squamous cell cancer. However, the nuclear localization sequence (NLS) of EGFR has not been extensively examined. In this study, we have shown that the juxtamembrane region of EGFR harbors a putative NLS with three clusters of basic amino acids (RRRHIVRKRTLRR (amino acids 645–657)) that mediates the nuclear localization of EGFR. We found that this newly characterized tripartite NLS is conserved among the EGFR family members (EGFR, ErbB2, ErbB3, and ErbB4) and is able to move each to the nucleus. Further, this tripartite NLS could also mediate the nuclear localization of other known cytoplasmic proteins such as pyruvate kinase. We have demonstrated that mutating one of the three basic amino acid clusters (R or K → A) leads to significant impairment of the nuclear localization of EGFR and that of a green fluorescent protein-pyruvate kinase-NLS reporter protein. Our results show that this tripartite NLS is distinct from the traditional mono- and bipartite NLS and reveal a mechanism that could account for the nuclear localization of membrane receptors.
We investigate the influence of vibronic coupling on a molecular dimer strongly coupled to a single cavity mode. In the framework of the Holstein‐Tavis‐Cummings model, the energy structure of the ...molecular dimer is analyzed by numerical exact diagonalization and perturbation theory. Under numerical exact diagonalization, we find that the degeneracy of lower polaritons vanishes in the presence of vibronic coupling. Under the second‐order degenerate perturbation theory, the degeneracy breaking of lower polaritons can be associated with asymmetric indirect interactions mediated by the upper polaritons and the dark states. The consistency of the two approaches confirms the robustness of our simulations, indicating that the vibration‐induced symmetry breaking should be experimentally observed.
The demonstration of vibration‐induced symmetry breaking on the energy‐level diagram of the molecular dimer under strong light‐matter interaction. The solid and dashed lines show the comparison of exact numerical diagonalization and perturbation analysis. The consistency of the two approaches confirms the robustness of our discoveries, indicating that the vibration‐induced symmetry breaking should be experimentally observed.
The human body is colonized by a wide range of microorganisms. The field of viromics has expanded since the first reports on the detection of viruses via metagenomic sequencing in 2002. With the ...continued development of reference materials and databases, viral metagenomic approaches have been used to explore known components of the virome and discover new viruses from various types of samples. The virome has attracted substantial interest since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic. Increasing numbers of studies and review articles have documented the diverse virome in various sites in the human body, as well as interactions between the human host and the virome with regard to health and disease. However, there have been few studies of direct causal relationships. Viral metagenomic analyses often lack standard references and are potentially subject to bias. Moreover, most virome-related review articles have focused on the gut virome and did not investigate the roles of the virome in other sites of the body in human disease. This review presents an overview of viral metagenomics, with updates regarding the relations between alterations in the human virome and the pathogenesis of human diseases, recent findings related to COVID-19, and therapeutic applications related to the human virome.
Because imbalanced power will cause the loss of the propulsion motor of the railway vehicle, and the increase in temperature will shorten the service life of the electric vehicle. Not only this but ...also increase the cost of electricity and maintenance. In the past, the industry only focused on methods to improve power quality such as load capacity, relay setting, and harmonic resolution. Now, the consider of three-phase unbalance rate (TPUR) must be applied. I propose special transformers wiring (STW) to improve the three unbalance rates and provide different transformer wiring methods. According to the IEEE Committee, in the future, power companies will need to install balanced relay stations to improve three-phase unbalance rate. The internal regulations of Taipower must be less than 4.5% (voltage unbalance rate (NPSUR) of 2.5% and motor temperature rise of 12.5%).
The derivation of the transformer “three-phase unbalance rate” model is the focus of the railway system. This research is based on the model derivation of different wiring methods to improve the problem caused by the three-phase imbalance and improve the using life of the train. They pointed out that Scott, Le-Blanc, and Modified-Woodbridge, the three wiring methods can be applied to future railway system and reduce the three-phase unbalance rate. They are in line with the IEEE standard (
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Certain immune cells and inflammatory cytokines are essential components in the tumor microenvironment to promote breast cancer progression. To identify key immune players in the tumor ...microenvironment, we applied highly invasive MDA-MB-231 breast cancer cell lines to co-culture with human monocyte THP-1 cells and identified CXCL7 by cytokine array as one of the increasingly secreted cytokines by THP-1 cells. Further investigations indicated that upon co-culturing, breast cancer cells secreted CSF1 to induce expression and release of CXCL7 from monocytes, which in turn acted on cancer cells to promote FAK activation, MMP13 expression, migration, and invasion. In a xenograft mouse model, administration of CXCL7 antibodies significantly reduced abundance of M2 macrophages in tumor microenvironment, as well as decreased tumor growth and distant metastasis. Clinical investigation further suggested that high CXCL7 expression is correlated with breast cancer progression and poor overall survival of patients. Overall, our study unveils an important immune cytokine, CXCL7, which is secreted by tumor infiltrating monocytes, to stimulate cancer cell migration, invasion, and metastasis, contributing to the promotion of breast cancer progression.
Nanocasting technique was used to obtain a biomimetic superhydrophobic electroactive polyimide (SEPI) surface structure from a natural Xanthosoma sagittifolium leaf. An electroactive polyimide (EPI) ...was first synthesized through thermal imidization. An impression of the superhydrophobic Xanthosoma sagittifolium leaf was then nanocasted onto the surface of the EPI so that the resulting EPI was superhydrophobic and would prevent corrosion. Polydimethylsiloxane (PDMS) was then used as a negative template to transfer the impression of the superhydrophobic surface of the biomimetic EPI onto a cold-rolled steel (CRS) electrode. The superhydrophobic electroactive material could be used as advanced coatings that protect metals against corrosion. The morphology of the surface of the as-synthesized SEPI coating was investigated using scanning electron microscopy (SEM). The surface showed numerous micromastoids, each decorated with many nanowrinkles. The water contact angle (CA) for the SEPI coating was 155°, which was significantly larger than that for the EPI coating (i.e., CA = 87°). The significant increase in the contact angle indicated that the biomimetic morphology effectively repelled water. Potentiodynamic and electrochemical impedance spectroscopic measurements indicated that the SEPI coating offered better protection against corrosion than the EPI coating did.
This paper is the first of a two-part study to investigate two rain-producing episodes in the longitudetime (Hovmoller) space upstream from Taiwan during the eighth intensive observing period (IOP-8, ...1217 June 2008) of the Southwest Monsoon Experiment/Terrain-influenced Monsoon Rainfall Experiment (SoWMEX/TiMREX), with a goal to better understand the mechanism and controlling factors for their organization and propagation. Both in a prefrontal environment, the first episode moved eastward and the second was a rare westward-moving event, and each caused heavy rainfall in Taiwan, on 14 and 16 June, respectively. In Part II, the roles played by synoptic conditions and terrain effects are further examined through sensitivity tests.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To explore non-adiabatic effects caused by electromagnetic (EM) vacuum fluctuations in molecules, we develop a general theory of internal conversion (IC) in the framework of quantum electrodynamics ...and propose a new mechanism, “quantum electrodynamic internal conversion” (QED-IC). The theory allows us to compute the rates of the conventional IC and QED-IC processes at the first-principles level. Our simulations manifest that, under experimentally feasible weak light–matter coupling conditions, EM vacuum fluctuations can significantly affect IC rates by an order of magnitude. Moreover, our theory elucidates three key factors in the QED-IC mechanism: the effective mode volume, coupling-weighted normal mode alignment, and molecular rigidity. The theory successfully captures the nucleus–photon interaction in the factor “coupling-weighted normal mode alignment”. In addition, we find that molecular rigidity plays a totally different role in conventional IC versus QED-IC rates. Our study provides applicable design principles for exploiting QED effects on IC processes.
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